Yeast: toasting the end

Yeast research as we know it will end with the solving of the organism on April 1, 2007, give or take 8.37 days. So said Mark Johnston, president of the Genetics Society of America, presenting on the future of the model organism at the biannual Yeast Genetics and Molecular Biology meeting this past month in Seattle. In combing through the Yeast Proteome Database, he found that so-called known yeast genes have followed a remarkably linear upward trajectory, reaching 4,679 as of the end of July of this year. A continuation of that trend, says Johnston, of Washington University in St. Louis, will mean that the organism's 6,000 genes will be known by April Fool's Day 2007. The prediction has inherent flaws and implied cheek. Budding grad students need not fear; even a 'known' gene can still be pretty mysterious. The University of Toronto's Tim Hughes put things into perspective; he says that Mark Robinson, a data analyst in his lab, spent a few weeks querying Medline to find what many might have suspected, that two-thirds of the genes may indeed be known. He confirmed this by abstract searches that included each of the 6,000 yeast-gene names (and their aliases) in conjunction with the word "cerevisiae" or "yeast." But, 50% of the papers were on a mere 10% of the genes. The disparity mirrors a divide in the yeast community. A few researchers take genomic approaches to find out a little about many genes at once, while more scientists focus their work on a particular gene or pathway. Global information feeds the more directed researchers, whose questions, hypotheses, and innovations feed back into the high-throughput technology. The loop is best demonstrated in the wealth of resources available to so-called yeast people, far more than those enjoyed by the Drosophila, C. elegans, or mouse communities. From mass spectra, to two-hybrid interactions, to protein and sequence microarray analyses, and even images of organismal morphology, yeast people are swathed in information. Add to that the physical resources: chips, reagents, plasmids, and mutant strains, including the resource to end all resources: a set of strains carrying deletions for practically every nonessential gene. But the glut of resources may serve as a harbinger of the end. Dan Gottschling, at the Fred Hutchinson Cancer Research Center in Seattle, says that discussions with grad students at the meeting worried him. Many were afraid that the interesting questions in yeast were drying up, making it a less attractive model for study. And for senior researchers working on more directed studies, the available resources breed a sense of entitlement. A session on yeast resources, opened to audience participation, drew many requests for better controls or data sets tailored to specific needs. Some provided stinging gripes about false-positive results, and requests for new resources ranged from a collection of temperature-sensitive alleles for all essential genes, to a request for monoclonal antibodies raised for every yeast protein. An almost palpable tension is surfacing. "It's definitely a tension we feel at [the Saccharomyces Genome Database] because we want to cater to both groups," says Eurie Hong, lead scientific curator at the database, which stores and freely distributes yeast genome data. Gottschling says it's a friction with somewhat deeper roots. "It speaks to the sociology around the whole system, the dynamic of someone who has spent their whole life working on the details and the new guy working on the technology to free us from those chains." But at meetings like this the groups break bread, drink beer, and extol the virtues of APYG (the awesome power of yeast genetics). In truth, the demands and requests are so great because projects seemingly unapproachable in other organisms are quite easy in the tiny eukaryote. "It's not impossible to make these things in the mouse; it just costs 100 times as much," Hughes says. And while Johnston admitted that his prediction about "solving" the organism tastes best with salt, he implored researchers to strive to understand in a meaningful way how each yeast gene and each network of genes fits together to create the whole. Such a systems-level understanding has been within reach for other communities, but for reasons that may have included a lack of funding or interest, the task was dropped. "Don't abandon it like the E. coli guys," Johnston urged. - Brendan A. Maher

Yeast: toasting the end

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Brendan Maher

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August 2004

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